What is the best management approach for an elderly female patient with hypertension, impaired renal function, and proteinuria, who is intolerant to calcium channel blockers like Norvasc (amlodipine) and currently on lisinopril 10 mg?

Management Approach for Elderly Female with Hypertension, CKD, and Proteinuria

Increase the lisinopril dose to at least 20-40 mg daily and add a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily) to optimize blood pressure control and provide renoprotection in this patient with significant proteinuria and declining renal function. 1

Immediate Priorities

This patient has experienced a dramatic decline in kidney function (eGFR 81→43 mL/min/1.73m²) with severe proteinuria (UACR 503 mg/g), placing her at very high cardiovascular and renal risk. The current lisinopril dose of 10 mg is subtherapeutic for both blood pressure control and renoprotection. 1

Why Maximize ACE Inhibitor Therapy

• ACE inhibitors are the cornerstone of treatment for patients with CKD and proteinuria ≥300 mg/day, as they reduce intraglomerular pressure and slow progression of kidney disease 1, 2
• Lisinopril remains effective and safe in patients with eGFR 30-60 mL/min without dose adjustment 3, 4
• Studies demonstrate that lisinopril at doses of 10-40 mg daily effectively controls blood pressure in patients with impaired renal function (GFR as low as 10-60 mL/min) 4, 5
• Expect a 20-30% increase in serum creatinine after ACE inhibitor initiation or uptitration—this reflects reduced intraglomerular pressure and is acceptable if stable 1, 3

Add Diuretic Therapy

Chlorthalidone 12.5-25 mg daily is the preferred diuretic for this patient: 1

• Patients with resistant or uncontrolled hypertension frequently have occult volume expansion that responds to diuretic therapy 1
• Chlorthalidone provides superior 24-hour blood pressure control compared to hydrochlorothiazide and was used in major outcome trials 1
• Thiazide-like diuretics remain effective at eGFR 30-45 mL/min, though loop diuretics become necessary when eGFR falls below 30 mL/min 1
• The combination of ACE inhibitor plus thiazide diuretic is consistently more effective than other two-drug combinations 1

Blood Pressure Target

Target systolic BP 130-139 mmHg in this elderly patient with CKD: 1

• The 2024 ESC guidelines recommend systolic BP 130-139 mmHg for patients with CKD 1
• The 2017 ACC/AHA guidelines support BP <130/80 mmHg for CKD patients based on SPRINT data, which included 28% of patients with stage 3-4 CKD 1
• More lenient targets (e.g., <140 mmHg) should be considered if the patient is ≥85 years or has symptomatic orthostatic hypotension 1

Monitoring Protocol

Check serum creatinine, potassium, and eGFR within 1-2 weeks after medication changes: 6, 3

• Discontinue ACE inhibitor only if: 1, 3

  • Serum creatinine increases >30% from baseline
  • Refractory hyperkalemia develops (K+ >5.5-6.0 mEq/L despite management)
  • Continued decline in kidney function after initial dip

• Monitor potassium closely as ACE inhibitors combined with thiazide diuretics can cause either hyperkalemia or hypokalemia 3

• Recheck labs at 1 month, then every 3 months once stable 6

Critical Pitfalls to Avoid

Do NOT combine ACE inhibitor with ARB or direct renin inhibitor—this increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 1, 3

Do NOT stop the ACE inhibitor prematurely due to modest creatinine elevation—up to 30% increase is expected and acceptable if it stabilizes 1

Avoid NSAIDs completely in this patient, as they will worsen renal function and blunt the antihypertensive effect of lisinopril 3

Monitor for orthostatic hypotension given her elderly status and inability to tolerate calcium channel blockers—check standing blood pressures at each visit 7

Alternative if ACE Inhibitor Intolerance Develops

If the patient develops ACE inhibitor-related cough or angioedema (rare but serious):

• Switch to an ARB (losartan 25-100 mg daily), which provides equivalent renoprotection with lower risk of cough 1, 2
• ARBs demonstrated significant proteinuria reduction (approximately 24%) independent of blood pressure lowering in patients with CKD 2
• Start at low dose and titrate based on BP response and tolerability 7

Why Not Calcium Channel Blockers

The patient is already documented as intolerant to amlodipine (Norvasc). While CCBs effectively lower blood pressure, they provide inferior renoprotection compared to ACE inhibitors/ARBs in patients with significant proteinuria: 2, 8

• Head-to-head trials show ACE inhibitors reduce proteinuria significantly while CCBs do not 2, 8
• In patients with proteinuria ≥1 g/day, enalapril reduced protein excretion by 270 mg/day while amlodipine showed no significant reduction 8